Robotic filling systems and methods

ABSTRACT

Systems and methods are disclosed, which permit filling containers with a product. A filling arm is disposed within a chamber and an optical sensor is configured to sense openings of the containers within the chamber. Locations of the sensed openings are used to guide the filling arm to fill the containers with a product.

RELATED APPLICATION

This application is a continuation of U.S. patent application Ser. No.13/744,408 filed Jan. 17, 2013, which is a divisional of U.S. patentapplication Ser. No. 12/393,183 filed Feb. 26, 2009 and claims thebenefit of U.S. Provisional Patent Application Ser. No. 61/033,682,filed Mar. 4, 2008, which applications are all incorporated herein byreference in their entirety.

BACKGROUND

By its very nature, the production of sterile pharmaceuticals by humanscan be problematic. Humans can be a large source of microbialcontamination. Also, with increased potencies, some drugs can behazardous in occupational exposure. For at least these reasons, roboticscan be used in dosage manufacturing to limit human contact. Isolatortechnology, which provides a solid barrier between a process and humans,can also be used in dosage manufacturing to limit human contact.

To enable sterile processing, isolator technology adapted various vaporand gas sterilization systems, bringing about an advance in asepticprocessing. Articulated cleanroom robots have been employed whichutilize internal negative pressure with an exhaust to generate cleanroomcapability. With the chemical sterilization and handling of potent drugswithin the isolator, an internal negative pressure cleanroom with anexhaust is not feasible, due largely to the leakage potential.

Sterile manufacturing is performed by various companies, oftenoutsourced companies, including small cleanroom facilities and largepharmaceutical facilities. Often, small cleanroom facilities are notoptimally equipped for pharmaceutical filling operations, which can leadto a lower quality product and higher risk for the outsourcing company.Conversely, large pharmaceutical facilities with high-speed linesgenerally can produce a higher quality product, but have relativelylimited flexibility with respect to batch size, variations of product,and timing.

OVERVIEW

The present inventors have recognized, among other things, that thereexists a need for a filling system that allows for increased flexibilitywhile, at the same time, allowing for increased quality of product.

In some embodiments, systems permit filling containers with a product. Afilling arm is disposed within the chamber. An optical sensor isconfigured to sense openings of the containers within the chamber.Locations of the sensed openings are used to guide the filling arm tofill the containers with a product.

In some embodiments, methods permit filling containers with a product.Openings of the containers are optically sensed. The containers arefilled with the product using locations of the sensed openings of thecontainers.

In some embodiments, systems permit filling containers with a product. Achamber is configured to maintain an environmental condition. A fillingarm is disposed within the chamber. A sensor is configured to senseopenings of the containers within the chamber. Locations of the sensedopenings are used to guide the filling arm to fill the containers with aproduct.

BRIEF DESCRIPTION OF THE DRAWINGS

The drawings illustrate generally, by way of example, but not by way oflimitation, various embodiments discussed in the present document.

FIG. 1 is a perspective view of a robotic filling system according tosome embodiments of the disclosed subject matter.

FIG. 2 is a top cutaway view of a robotic filling system according tosome embodiments of the disclosed subject matter.

FIG. 3 is a perspective view of a robotic arm and a port of a roboticfilling system according to some embodiments of the disclosed subjectmatter.

FIG. 4 is a perspective view of a robotic arm and a port of a roboticfilling system according to some embodiments of the disclosed subjectmatter.

FIGS. 5A and 5B are perspective views of a filling arm of a roboticfilling system according to some embodiments of the disclosed subjectmatter, the filling arm filling containers.

FIG. 6 is a perspective view of a stopper disc stack of a roboticfilling system according to some embodiments of the disclosed subjectmatter.

FIG. 7 is an exploded view of a stopper disc stack of a robotic fillingsystem according to some embodiments of the disclosed subject matter.

FIG. 8 is a perspective view of a stopper disc stack of a roboticfilling system according to some embodiments of the disclosed subjectmatter.

FIG. 9 is a perspective view of a stopper disc stack of a roboticfilling system according to some embodiments of the disclosed subjectmatter.

FIGS. 10A and 10B are perspective views of a stopper disc stack of arobotic filling system according to some embodiments of the disclosedsubject matter, the stopper disc stack within a transfer container.

FIG. 11 is a cross-sectional view of stoppers held within a portion of astopper disc stack of a robotic filling system according to someembodiments of the disclosed subject matter.

DESCRIPTION

The present inventors have recognized, among other things, that thereexists a need for a filling system that allows for increased flexibilitywhile, at the same time, allowing for increased quality of product. Thepresent inventors have developed systems and methods for fillingcontainers with products, which, as described in more detail below,allow for increased flexibility and increased quality.

Referring to FIGS. 1 and 2, in an example, a filling system 10 isconfigured to fill containers 90 with a product. In one example, theproduct is a liquid product. In another example, the product is apharmaceutical product. In another example, the product is potentiallytoxic or otherwise harmful. As will be described in more detail below,the filling system 10 can be configured to locate, target, and fillrandomly placed containers 90 within a tray 80 or nest, without the needfor mechanical container handling parts, or other change parts forfilling equipment. Many types of containers 90 are contemplated herein,including, but not limited to vials, syringes, bottles, beakers, testtubes, etc.

In one example, the filling system 10 includes a chamber 20 configuredto maintain desired environmental conditions. In one example, thechamber 20 is an isolator chamber capable of maintaining an asepticenvironment within the chamber 20. The chamber 20, in one example,includes one or more ports 22 for access to the interior of the chamber20. In one example, the port 22 is a rapid transfer port to allow foraseptic transfer of articles from a container, such as a transferisolator, to the chamber 20. Briefly, in one example, the rapid transferport 22 can be configured to mate with a door of the container such thatthe unsterilized exterior surfaces mate against and attach to each otherbefore opening, such that, when the port 22 and door combination isopened, the unsterilized exterior surfaces of the door and port 22 arecontained against each other, thereby limiting contamination of theinterior environments of the container and the chamber 20. The fillingsystem 10 can include proximity sensors or other such devices to sensewhen a container or transfer isolator is engaged with the port 22. Inthis way, opening of the port 22 while not engaged with a container ortransfer isolator, and, in turn, contamination of the interiorenvironmental conditions, can be guarded against. The ports 22 aredescribed in more detail below.

In one example, the chamber 20 includes one or more glove holes 21disposed in the walls of the chamber 20. The glove holes 21 can be usedto manually manipulate objects within the chamber 20 without opening thechamber 20 or otherwise compromising the environmental conditions withinthe chamber 20.

In one example, a filling arm 40 is disposed within the chamber 20. Thefilling arm 40, in one example, is a robotic arm. The filling arm 40includes filling tubing 42 extending from a pump unit 44 to a point atan end of the filling arm 40. In one example, an outlet of the fillingtube 42 includes a valve, filling needle, or other flow controllingdevice to control discharge of the product from the filling tubing 42.In one example, the filling tubing 42 extends from the reservoir andthrough the pump 44. The pump 44 is configured to selectively urge theproduct from a reservoir, through the filling tubing 42, and into thecontainers 90. In one example, the pump 44 is a peristaltic pump, suchas a rotary or a linear peristaltic pump. As will be described in moredetail below, the filling arm 40 positions the outlet of the fillingtubing 42 over each container 90 to allow filling of the containers 90with product.

The filling system 10, in some examples, includes a sensor 12 forsensing the containers 90 within the chamber 20. In one example, thesensor 12 senses openings of the containers 90. In other examples, thesensor 12 is an optical sensor, a camera system, or a laser system. Thesensor 12, in one example, is mounted at a top surface of the chamber 20and is positioned to sense an area within the chamber 20, as portrayedby a sensing cone 14. For instance, the optical sensor 12 can beconfigured to locate containers 90 within the sensing cone 14 and targetcenters of the openings of the containers 90. The locations of thesensed openings of the containers 90 are used to guide the filling arm40 to fill the containers 90 with product. In one example, the targetedcenters are used by a controller for controlling the filling arm 40. Inone example, the optical sensor 12 is configured to perform a pre-fillinspection of containers 90 to determine if any containers are defectiveor otherwise unfit for filling. If such a defective container is found,the container can be ignored during the filling process so as to reducewaste of product and limit potential leakage.

In one example, a holding arm 30 is disposed within the chamber 20 fortransporting and holding the containers 90 within the chamber 20. Thechamber 20, in one example, includes a stoppering arm 50 configured tostopper or otherwise close the openings of the containers 90. Theseaspects of the filling system 10 are discussed in greater detail below.

In some examples, one or more of the holding arm 30, filling arm 40, andstoppering arm 50 are servo-driven robotic arms. In other examples, thearms 30, 40, 50 can be of differing configurations, provided they arecapable of functioning in the manners described herein.

Referring now to FIGS. 3, 4, 5A, and 5B, the holding arm 30 can be usedto perform multiple tasks, including, for instance, opening doors 28 ofports 22 and transporting and holding containers 90. The holding arm 30,in one example, includes a generally U-shaped end effect tool 32. In oneexample, the end effect tool 32 includes a hole 32A on one “leg” of theU-shaped tool 32, a hook 32B on the other “leg” of the U-shaped tool 32,and a shoulder 32C around an interior edge of the tool 32. In otherexamples, the end effect tool can include different configurationsdepending upon the interactions and tasks required of the holding tool.

The hole 32A and the hook 32B are configured to allow the holding arm 30to open and close the ports 22 to allow for containers 90 to enter andexit the chamber 20. For instance, a transfer isolator or other suchcontainer can be used to transfer sterilized containers into the chamber20. In one example, once a transfer isolator or other container isattached to the port 22, as signaled by the proximity sensor or othersuch device, the controller can control the holding arm 30 to open theport 22.

As shown in FIG. 3, the hole 32A is configured to selectively engagewith a post 25A of a clamp handle 23 to allow the holding arm 30 tomanipulate the clamp handle 23. Pivoting of the clamp handle 23 to anunlocked position (FIG. 4) releases posts 27 of the door 28 to allow thedoor 28 to be opened. In one example, the clamp handle 23 includes a pin25B, which is engageable within a clasp 26 to maintain the clamp handle23 in the unlocked position.

Once the clamp handle 23 is in the unlocked position, the hook 32B ofthe holding arm 30 can be used to interact with a handle 24 of the door28 to pivot the door 28 to an open position. As described above, thedoor of the container or transfer isolator can be engaged with the door28 to open with the door 28, thereby allowing the holding arm 30 toaccess the interior of the transfer isolator or container, whilegenerally maintaining the desired environmental conditions within thechamber 20. In one example, the containers 90 are held on a tray 80 orother such holder configured to allow the holding arm 30 to pick up thetray 80 using the shoulder 32C. In this example, the tool 32 is extendedinto the transfer isolator or container and positioned such that theshoulder 32C of the tool 32 abuts a bottom side of a rim of the tray 80.The holding arm 30 can then pick up the tray 80 to transport it into thechamber 20. Once the tray 80 is transported within the chamber 20, inone example, the port 22 can be closed by the holding arm 30 in areverse manner to that described above to open the port 22. In anotherexample, the port 22 can remain open, for instance, to replace the tray80 of containers 90 once the containers 90 have been filled. In anotherexample, once the containers 90 have been filled, the holding arm 30 canbe used to open a port 22, as described above, and to place the tray 80of filled containers 90 within a transfer isolator or other containerengaged thereto for removal of the filled containers 90 from within thechamber 20.

Referring to FIGS. 2, 5A, and 5B, in one example, once the tray 80 isreceived by the tool 32, the holding arm 30 transports the tray 80 to afilling position within the chamber 20. In one example, the fillingposition is a location within the chamber 20 that is within the sensingcone 14 and within reach of the filling arm 40. Once the tray 80 ofcontainers 90 is in the filling position, the sensor 12, for instance anoptical sensor, can be activated to locate the containers 90 and targetthe openings of the containers 90. In one example, pattern recognitionsoftware is employed to analyze data from the sensor 12 to identifysuitable filling locations corresponding to the openings of thecontainers 90 within the chamber 20. In this way, the containers 90 invarious positions on the tray 80, including random positions, can belocated and targeted by the sensor 12 and pattern recognition softwareand need not be positioned with any particular pattern or spacing.Additionally, such locating and targeting can be performed regardless ofthe size of the containers 90. In one example, as shown in FIG. 5A,containers 90 of a first size are located and targeted. In anotherexample, as shown in FIG. 5B, containers 90′ of a second size arelocated and targeted. The pattern recognition software, in one example,is implemented in the controller of the filling system 10. In anotherexample, the pattern recognition software is implemented in a computeror control module different from the controller of the filling system10.

In one example, the positions of the containers 90 are used to controlthe filling arm 40 to travel to the predetermined filling locations anddispense the product into the containers 90, 90′. In one example, thepositions of the containers 90 are also used to control the stopperingarm 50, which picks up a closure for the container 90, 90′ and places itinto the opening of the container 90, 90′, as described in more detailbelow.

Referring to FIGS. 6, 7, and 11, in one example, the stoppering arm 50is configured to pick up and place stoppers 92 or other closures in theopenings of the containers 90. Closures contemplated for use with thefilling system 10 include lyophilization stoppers, serum stoppers,syringe stoppers, and the like. In some examples, the stoppering arm 50includes a gripping implement 53 at the end thereof. In one example, thestoppering arm 50 includes tubing 52 extending from a vacuum source toan end of the stoppering arm 50. In one example, the tubing 52 connectsto the gripping implement 53, the gripping implement 53 being actuatedby pulling of a vacuum through the tubing 52. In another example, thegripping implement includes mechanical grasping members, such asmechanically-actuated fingers or other such mechanical graspingmechanisms.

In one example, the stoppering arm 50 picks up stoppers 92 from astopper disc stack 60. In some examples, the stopper disc stack 60includes one or more stopper discs 62 stacked on a spindle 67 sandwichedbetween a top plate 66 and a bottom plate 68. The discs 68 are axiallyslidable along the spindle 67. In one example, a top nut 64 is disposedon the spindle 67 and acts to retain the top plate 66 on the spindle 67.In one example, the top nut 64 is integrally attached to the top plate66. In one example, the top nut 64 includes one of more handles 64A toallow for manual manipulation of the top nut 64. In one example, thespindle 67 includes first threads 67A, which engage the top nut 64 in afirst, closed position (see FIG. 8) where the top plate 66 is stacked ontop of the uppermost disc 62 and second threads 67B, which engage thetop nut 64 in a second, open position (see FIG. 9) to allow access tothe stoppers or other closures within the stopper disc stack 60.

In one example, the discs 62 are circular, although other shapes ofdiscs are contemplated. In one example, each of the discs 62 includes aplurality of recesses 62A configured to hold stoppers 92 or otherclosures therein. As shown in FIG. 11, the recesses 62A, in one example,do not extend through the entire disc 62 to allow for stoppers 92 to beseated within the recesses 62A but not fall through the disc 62. In afurther example, a hole 62C having a width smaller than the width of therecess 62A is disposed through the remainder of the disc 62 at thebottom of the recess 62A. The hole 62C allows for penetration ofsterilants, such as steam, ethylene oxide, and hydrogen peroxide vapor.Each of the discs 62 can include one or more feet 62B extending from abottom surface of the disc 62. The feet 62B abut the disc 62 below tocreate spacing between adjacent discs 62 in the stopper disc stack 60.In one example, each of the discs 62 can include indentations in a topsurface of the disc 62 which correspond to and accept the feet 62B.

The recesses 62A of stopper disc stack 60 provide positions to holdstoppers 92 or closures in place during movement and processing. Thediscs 62, in some examples, can be made of polymeric materials, such asPTFE, HDPE, LDPE, polyetherimide, polysulphone, polybenzimidazole,polyamide-imide, polyetherimide, polyimide, polyarylether ketones, orpolythermide, or metals, such as stainless steel, titanium, aluminum, orhastelloy. Also, in further examples, the metals can be coated orotherwise treated to provide a non-stick or decreased-stick surface,using, for instance, a hard annodization process or other such treatmentor coating processes. In one example, as shown in FIG. 11, each disc 62is machined or otherwise formed on a lower surface to produce aconvoluted surface 62D to maintain contact with stoppers 92 or otherclosures held by the disc 62 below. In one example, such contact inmaintained to a minimum to enable penetration of sterilants such assteam, ethylene oxide, and hydrogen peroxide vapor. In one example, thestopper disc stack 60 is compatible with sterilization by radiation,such as electron beam irradiation and gamma irradiation. In one example,the discs 62 cooperate to effectively surround the stoppers 92 or otherclosures between the sandwiched discs 62 to allow for containment of thestoppers 92 or other closures during multi-axis movement of the stopperdisc stack 60.

The stopper disc stack 60, in some examples, is disposed within thechamber 20 during container filling to provide stoppers 92 or otherclosures for closing the containers 90 after filling. In one example,the stopper disc stack 60 is placed on a rotating turntable within thechamber 20. The stopper disc stack 60 can include engagement features,such as, for instance, a notch 68A and a hole 68B in the bottom plate68, to engage the stopper disc stack 60 with the turntable so as torotate therewith, and to ensure that the stopper disc stack 60 is ableto be indexed for stopper 92 removal. It should be understood that theabove-described engagement features are not intended to be limiting andthat other engagement features are contemplated herein. In this way,rotation of the turntable causes rotation of the stopper disc stack 60.In one example, each of the discs 62 of the stopper disc stack 60 areable to rotate with the turntable due to the interaction of the feet 62Bon the bottom side of each of the discs 62 with the indentations in thetop side of each of the adjacent discs 62.

Referring now to FIGS. 1, 2, 10A, and 10B, the stopper disc stack 60 canbe introduced within the chamber 20 manually by a user. In someexamples, the stopper disc stack 60 can be introduced within the chamber20 without disrupting the environmental condition within the chamber 20.The stopper disc stack 60 can be transported, for instance, from anautoclave or from a storage location, to the filling system 10 using atransfer isolator 100 or other container. As described above, thetransfer isolator 100 or other container can be engaged with a port 22in the chamber 20. In one example, the transfer isolator 100 or othercontainer is engaged with the horizontally-oriented port 22 disposed ina floor of the chamber 20. In one example, the transfer isolator 100 orother container includes handles 102 to facilitate handling of thetransfer isolator 100 or other container and engagement of the transferisolator 100 or other container with the port 22, for instance. In oneexample, the transfer isolator 100 or other container includes tabs 104or other engagement features configured to interact with correspondingtabs or other engagement features associated with the port 22, such thatrotation of the transfer isolator 100 or other container with respect tothe port 22 engages the tabs 104 of the transfer isolator 100 or othercontainer with the engagement features of the port 22 to engage thetransfer isolator 100 or other container with the port 22. Once thetransfer isolator 100 or other container is engaged with the port 22,the user can manually open the door of the port 22 using the glove holes21 (FIG. 1), grasp the stopper disc stack 60 using the handles 64A ofthe top nut 64, lift the stopper disc stack 60 from the transferisolator or other container, and place the stopper disc stack 60 on theturntable within the chamber 20. Although introduction of the stopperdisc stack 60 is described as a manual process, it is contemplatedherein that the process can be automated.

Referring to FIGS. 6, 8, and 9, once placed on the turntable, the topnut 64 can be rotated to move the top nut 64 from the first, closedposition (FIG. 8) to the second, open position (FIG. 9), thereby liftingthe top plate 66 and allowing access to the stoppers or other closureswithin the stopper disc stack 60. In this way, the stoppering arm 50 cangain access to and pick up the stoppers or other closures for placementwithin the openings of the containers 90, as described above.

In one example, the turntable is rotated to rotate the stopper discstack 60 while the stoppering arm 50 is stoppering containers 90 toreduce the amount of movement of the stoppering arm 50. That is, byrotating the stopper disc stack 60, an awaiting stopper or other closurecan be moved to a position relatively close to location of thestoppering arm 50 within the chamber 20. Also, by rotating the stopperdisc stack 60, the number of pick-up or home locations for thestoppering arm 50 can be reduced. That is, one pick-up location can beprogrammed for each ring of recesses 62A in the discs 62, so that thedisc 62 can be rotated to place a recess 62A having a stopper or otherclosure therein at the pick-up location prior to the stoppering arm 50picking up a stopper. For instance, the discs 62 shown in FIG. 7 includefive generally concentric rings of recesses 62A, so five pick-uplocations can be programmed, one pick-up location corresponding to eachof the five rings of recesses 62A. Although discs 62 having five ringsof recesses 62A are shown and described, it is contemplated that thediscs include more or fewer than five rings of recesses, depending onclosure size, recess spacing, material requirements, and sterilizationrequirements, among other things.

In one example, once one ring of stoppers is exhausted, the pick-uplocation can be moved to another, unexhausted ring of stoppers. Inanother example, stoppers at the pick-up locations for each of the ringsat a particular rotational location of the disc 62 can be picked upbefore the disc 62 is rotated to place more stoppers in each of thepick-up locations.

Referring to FIGS. 2, 6, and 9, in one example, the filling system 10includes a disc holder arm 54 to pick up discs 62, for instance, afterall the stoppers or other closures have been removed therefrom to exposethe stoppers or other closures of the disc 62 below. In one example, thedisc holder arm 54 includes a shoulder 54A configured to fit betweenadjacent discs 62 and abut a bottom surface of the empty disc 62 to liftthe disc 62 from the disc 62 below. As portrayed in FIG. 9, the discholder arm 54, in one example, is rotated into position with theshoulder 54A disposed between two discs 62. The disc holder arm 54 isthen lifted toward the top plate 66 to separate the two discs 62 toallow for the stoppering arm 50 to access and pick up stoppers from thedisc 62 below. When the stoppers are exhausted from this disc 62, thealready-lifted disc 62 can be lowered back down, and the disc holder arm54 can be repositioned below the newly-exhausted disc 62 and raised tolift the two (or more) empty discs 62 and expose the stoppers of anotherdisc 62 until all of the stoppers of the stopper disc stack 60 areexhausted, at which point the stopper disc stack 60 can be replaced. Inother examples, the discs 62 can be raised or lowered by the disc holderarm 54 regardless of whether all of the stoppers are removed from a disc62. For instance, in one example, the disc holder arm 54 is used toexpose another disc 62 holding stoppers of a different size or adifferent material for containers of different sizes or containersfilled with products requiring different closure materials,respectively.

Accordingly, the above-described systems and methods allow for roboticfilling of containers. In one example, the system allows for the asepticfilling of vials and syringes, particularly for small and developmentalruns of potent and/or toxic materials. In one example, the systemsprovide an automated aseptic filling system that does not require theuse of unique or specialized components for various container sizes. Inone example, the system allows for filling of various sized or shapedcontainers, provided a recognizable container opening exists. Also, theoptical system can allow for inspection of containers prior to filling,thus reducing the possibility of rejection due to container defectspost-filling. Additionally, pre-fill inspection can be achieved with theoptical sensor without the use of additional parts or manual steps. Inone example, the systems are configured to be minimally disruptive tosterilized air flows commonly used in aseptic filling.

In this way, in some examples, randomly placed containers can be filledautomatically, potentially resulting in labor and time savings. Theoptical sensor system allows for precision targeting and filling ofcontainers, which can lead to reduced potential for spills of high-valueor toxic materials that could require containment. Because the fillingsystem, in some examples, is capable of handling various products andvariously sized and shaped containers, the filling system is relativelyrapidly adaptable for new products and processes. Also, by using opticalsensors in some examples, the system allows for reduction of productlosses due to inclusion of a pre-fill inspection of containers.Additionally, because the system is relatively small and contained, thesystem provides for relatively easy cleaning of surfaces and parts.Moreover, by being configured to accept variously sized and shapedcontainers, the system allows for reduced cost because little or nocontainer-specific parts are needed.

The above-described systems and methods also allow for roboticstoppering of containers. The discs, in some examples, are configured toallow penetration of sterilant to the closures held by the discs fromabove and below through the holes and convolutions of the discs. Thesandwiched discs of the stopper disc stack can be configured to allowthe closures to be sterilized and transferred on multiple axes withoutmovement of the closures within the stopper disc stack. The stopper discstack can be configured to allow for servo-actuated pick and placehandling, for instance using the stoppering arm, as part of theautomated filling system. The stopper disc stack also can be configuredto allow for automatic actuation for pick and placement of closures. Thestopper disc stack can be configured to be transferred through the useof transfer isolators or other such containers using ports, such asrapid transfer ports, to enable aseptic and contained transfers betweenrooms or barrier isolation systems. In some examples, the discs areconfigured to accommodate multiple closure types, includinglyophilization stoppers, serum stoppers, and syringe stoppers.

In this way, in some examples, the system can allow for the use ofrobotic filling in a discontinuous manner to produce sterilepharmaceutical products, reducing if not eliminating the need forconveyors, vibrating bowls, handling chutes, or other such closurehandling equipment. Additionally, the stopper disc stack allows forreduced manual handling during sterile operations, reducing thelikelihood of aseptic interventions in sterile processing. Also, thesystem allows for multiple stopper disc stacks to be sterilized off-lineand made available on a modular basis during filling operations.

Additional Notes

The above detailed description includes references to the accompanyingdrawings, which form a part of the detailed description. The drawingsshow, by way of illustration, specific embodiments in which theinvention can be practiced. These embodiments are also referred toherein as “examples.” Such examples can include elements in addition tothose shown and described. However, the present inventors alsocontemplate examples in which only those elements shown and describedare provided.

All publications, patents, and patent documents referred to in thisdocument are incorporated by reference herein in their entirety, asthough individually incorporated by reference. In the event ofinconsistent usages between this document and those documents soincorporated by reference, the usage in the incorporated reference(s)should be considered supplementary to that of this document; forirreconcilable inconsistencies, the usage in this document controls.

In this document, the terms “a” or “an” are used, as is common in patentdocuments, to include one or more than one, independent of any otherinstances or usages of “at least one” or “one or more.” In thisdocument, the term “or” is used to refer to a nonexclusive or, such that“A or B” includes “A but not B,” “B but not A,” and “A and B,” unlessotherwise indicated. In the appended claims, the terms “including” and“in which” are used as the plain-English equivalents of the respectiveterms “comprising” and “wherein.” Also, in the following claims, theterms “including” and “comprising” are open-ended, that is, a system,device, article, or process that includes elements in addition to thoselisted after such a term in a claim are still deemed to fall within thescope of that claim. Moreover, in the following claims, the terms“first,” “second,” and “third,” etc. are used merely as labels, and arenot intended to impose numerical requirements on their objects.

The above description is intended to be illustrative, and notrestrictive. For example, the above-described examples (or one or moreaspects thereof) may be used in combination with each other. Otherembodiments can be used, such as by one of ordinary skill in the artupon reviewing the above description. The Abstract is provided to complywith 37 C.F.R. § 1.72(b), to allow the reader to quickly ascertain thenature of the technical disclosure. It is submitted with theunderstanding that it will not be used to interpret or limit the scopeor meaning of the claims. Also, in the above Detailed Description,various features may be grouped together to streamline the disclosure.This should not be interpreted as intending that an unclaimed disclosedfeature is essential to any claim. Rather, inventive subject matter maylie in less than all features of a particular disclosed embodiment.Thus, the following claims are hereby incorporated into the DetailedDescription, with each claim standing on its own as a separateembodiment. The scope of the invention should be determined withreference to the appended claims, along with the full scope ofequivalents to which such claims are entitled.

1-41. (canceled)
 42. A system for filling containers with a product,comprising: an aseptic controlled environment chamber; a filling armdisposed within the chamber; and a sensor configured to sense openingsof the containers within the chamber, wherein locations of the sensedopenings are used to automatically guide the filling arm to fill thecontainers with product.
 43. The system of claim 42 wherein the sensorincludes an optical sensor.
 44. The system of claim 42 wherein thesensor includes a camera system.
 45. The system of claim 42 wherein thesensor includes a laser system.
 46. The system of claim 42 furthercomprising a stopper disk stack configured to hold stoppers for use inclosing openings of the containers, wherein the stopper disc stack isconfigured to be introduced within the chamber without disrupting theaseptic controlled environment chamber.
 47. The system of claim 42further comprising a first controller portion responsive to the sensorto identify locations of openings of the containers, and a secondcontroller portion responsive to the first controller portion and beingoperative to guide the filling arm to fill the containers.
 48. Thesystem of claim 47 wherein the first and second controller portions arepart of the same controller.
 49. The system of claim 47 wherein thefirst controller portion includes pattern recognition software.
 50. Thesystem of claim 42 further comprising an articulated holding armdisposed within the chamber including at least a first member and asecond member joined by an articulation, wherein the second memberincludes means for holding a group of containers.
 51. The system ofclaim 50 wherein the articulated holding arm has a range of motion thatallows the articulated holding arm to move the means for holding to aplurality of different positions in the chamber.
 52. The system of claim51 wherein the means for holding includes means for holding a tray. 53.The system of claim 52 wherein the sensor is configured to senseopenings of the containers disposed in a tray while the tray is beingheld by the means for holding a tray.
 54. The system of claim 50 whereinthe articulated holding arm includes a robotic apparatus.
 55. The systemof claim 50 further comprising a controller for operating thearticulated holding arm in response to the sensor.
 56. The system ofclaim 42 wherein the filling arm is an articulated filling arm includingat least a first member and a second member joined by an articulation,wherein the second member includes means for filling containers.
 57. Thesystem of claim 42 wherein the articulated filling arm has a range ofmotion that allows the articulated holding arm to move the means forfilling to fill the containers within the chamber.
 58. The system ofclaim 42 wherein the filling arm includes a servo-driven robotic arm.59. The system of claim 50 wherein the articulated holding arm includesa servo-driven robotic arm.